We have found that the cellular myc oncogene has been activated by chromosomal translocation in virtually all mouse plasmacytomas, implicating c-myc expression in tumor formation. The translocation links the c-myc oncogene to an immunoglobulin heavy chain gene in a head-to-head configuration that may be the result of an abortive switching event (Shen-Ong et al., Cell 31:443-452, 1982). Further studies have demonstrated that the translocation breakpoint occurs within the c-myc gene in most cases, leading to the transcriptional activation of sequences in the first intron that provide a bidirectional promoter (Keath et al., Cell 37:521-528, 1984). The level of c-myc expression in the tumor cells was found to be similar to that in proliferating normal cells, indicating that physiologically normal levels of the c-myc protein may be capable of contributing to cell transformation if expressed inappropriately. Studies of the sequences at several translocation breakpoints suggest that there may be a small conserved sequence that is preferentially utilized as a cleavage site within the c-myc gene (Piccoli et al., Nature, in press). More recently, we have studied established fibroblast lines that are expressing c-myc genes under the control of viral promoters (KeatH et al., submitted for publication). These cells were found to be tumorigenic in nude mice, while exhibiting only slight alterations in cell growth and morphology. Interestingly, the normal c-myc gene was expressed in subconfluent cells in culture but was shut off in the nude mouse tumors, where only the c-myc genes linked to the viral promoters were expressed. Thus the translocation of the c-myc gene almost certainly contributes to the transformation of plasmacytoma cells and other tumor cells in which the gene is transcriptionally activated. (X)